{"id":34375,"date":"2018-06-29T08:32:31","date_gmt":"2018-06-29T08:32:31","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=34375"},"modified":"2018-06-29T09:39:10","modified_gmt":"2018-06-29T09:39:10","slug":"rifabutin-dosed-2-5-mgkg-daily-with-lopinavirr-in-children-achieves-comparable-exposure-to-adults","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/34375","title":{"rendered":"Rifabutin dosed 2.5 mg\/kg daily with lopinavir\/r in children achieves comparable exposure to adults\u00a0"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/span><\/strong><\/p>\n

In children, rifabutin 2.5 mg\/kg daily with lopinavir\/ritonavir co-treatment achieved AUC0\u201324 comparable to adults. Serious adverse events were rare and HIV and TB outcomes were favourable. Neutropenia was rare, mild, and improved with ongoing rifabutin treatment. <\/span>\u00a0<\/span><\/strong><\/p>\n

These findings from an interim analysis of a pharmacokinetic (PK) study conducted in coinfected Nigerian children were presented at the 19th International Workshop on Clinical Pharmacology. <\/span><\/p>\n

Treatment options are lacking for HIV\/TB coinfected children needing protease inhibitor (PI)-based ART. Rifabutin (RBT) is the preferred rifamycins for adults receiving PIs.<\/span><\/p>\n

Only one previous study looked at RBT PK in children on PIs. It was stopped early after two of six children developed grade 4 neutropenia.<\/span><\/p>\n

The Nigerian study evaluated PK of RBT in children aged 3\u201315 years receiving lopinavir\/ritonavir (LPV\/r)-based ART and RBT 2.5 mg\/kg daily-containing TB treatment over 48 weeks. Intensive 24-hour PK sampling was performed at 2, 4, and 8 weeks after starting RBT. <\/span><\/p>\n

At interim analysis, 8 children (75% male), median age 13.5 years (IQR 12.8\u201314.3) and weight 28.5 kg (IQR 24.1\u201332.1) had 20 PK visits. <\/span><\/p>\n

The median RBT AUC0-24 was 4.77 ug*h\/mL (IQR 3.84-6.75). Three participants had an AUC0-24 less than 3.2 ug*h\/mL at week 2; but all were above 3.8 ug*h\/mL (comparator: adults receiving RBT 300 mg daily without ART) at the 4 and 8 week visits. <\/span><\/p>\n

Serious adverse events were uncommon: of 407 follow-up laboratory results, grade 3 and 4 abnormalities were reported in 11 (3%) and 2 (0.5%) cases, respectively. <\/span><\/p>\n

Grade 3 neutropenia occurred on 3 occasions, and resolved without stopping RBT in all cases. Anaemia was the most common adverse event. No discontinuations due to ART or TB treatment were reported.<\/span><\/p>\n

The investigators reported that the children are doing well clinically with six of seven achieving viral load suppression to less than 1000 copies\/mL and resolution of TB symptoms at six months.<\/span><\/p>\n

Enrollment into this study (n=15) is now complete and an additional study is now underway in young children aged 12\u201336 months. <\/span><\/p>\n

Reference<\/span><\/p>\n

Rawizza H et al. Rifabutin PK and safety among HIV\/TB coinfected children receiving lopinavir.19th International Workshop on Clinical Pharmacology, 22\u201324 May 2018, Baltimore. Oral abstract 13.
\n<\/span>http:\/\/regist2.virology-education.com\/presentations\/2018\/Antiviralpk\/30_rawizza.pdf<\/a> (PDF)<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base In children, rifabutin 2.5 mg\/kg daily with lopinavir\/ritonavir co-treatment achieved AUC0\u201324 comparable to adults. Serious adverse events were rare and HIV and TB outcomes were favourable. Neutropenia was rare, mild, and improved with ongoing rifabutin treatment. …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,34,37],"tags":[254],"class_list":["post-34375","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-pk-and-drug-interactions","category-tb-coinfection","tag-pk-workshop-2018"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34375","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=34375"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34375\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=34375"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=34375"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=34375"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}